Adjuvant Bevacizumab May Not Improve Overall Survival in Resected Melanoma
Previous studies have demonstrated that the vascular endothelial growth factor inhibitor bevacizumab is active in melanoma, and may be effective in the maintenance setting.
Adjuvant bevacizumab may prolong the disease-free interval (DFI) among patients with melanoma post-resection, but may not have any significant effects on survival outcomes, according to a study published in the Annals of Oncology.1
Vascular endothelial growth factor (VEGF), a key driver of angiogenesis, is highly prevalent in melanoma and has been associated with poorer outcomes. Previous studies have demonstrated that the VEGF inhibitor bevacizumab is active in melanoma, and may be effective in the maintenance setting.
For the AVAST-M phase 3 study, researchers randomly assigned 1343 patients with completely resected high-risk cutaneous melanoma to receive adjuvant bevacizumab 7.5 mg/kg 3 times a week for 1 year or to standard observation. Patients were stratified according to primary tumor Breslow thickness, N stage, primary tumor ulceration status, and gender. Laboratory values, specifically plasma lactate dehydrogenase (LDH) and VEGF and VEGF receptor1 (VEGFR1), were assessed at baseline.
After a median follow-up of 6.4 years, 38% (254) and 39% (261) of patients in the bevacizumab and observation arm had died, respectively, and 50% (336) and 55% (371) of patients had experienced disease recurrence, respectively.
Results showed that there were no significant differences between the 2 arms in regards to overall survival (OS) or distant metastasis-free interval (DMFI). The 5-year OS rate was 64% among patients in both study arms (hazard ratio [HR], 0.98; 95% CI, 0.82-1.16; P = .78), and the 5-year DMFI was 58% among patients treated with bevacizumab compared with 54% among patients in the observation arm (HR 0.91; 95% CI, 0.78–1.07; P = .25).
The disease-free interval (DFI), however, was significantly improved; 51% of patients in the bevacizumab arm were disease free compared with 45% of patients in the observation arm after years (HR, 0.85; 95% CI, 0.74-0.99; P = .03).
Further analysis revealed that patients with a BRAFV600 mutation had significantly poorer OS compared to BRAF wild-type patients in the observation arm (P = .06); patients with the BRAFV600 mutation may experience an OS benefit when maintained with bevacizumab (P = .21). Baseline LDH levels, which may be predictive of outcomes in metastatic disease, were not found to be prognostic of OS, DMFI, or DFI after resection.
Adjuvant bevacizumab may improve DFI but not OS, leading the authors to conclude that “adjuvant bevacizumab cannot be recommended as a standard adjuvant therapy after resection of melanoma at high risk of recurrence.”
- Corrie PG, Marshall A, Nathan PD, et al. Adjuvant bevacizumab for melanoma patients at high risk of recurrence: survival analysis of the AVAST-M trial. Ann Oncol. 2018;28(9):1843-1852. doi: 10.1093/annonc/mdy229